Phase I trial and pharmacokinetics of gemcitabine in children with advanced solid tumors

J Clin Oncol. 2004 Jun 15;22(12):2445-51. doi: 10.1200/JCO.2004.10.142.


Purpose: To determine the maximum tolerated dose, toxicity, and pharmacokinetics of gemcitabine in children with refractory solid tumors.

Patients and methods: Gemcitabine was given as a 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks, to 42 patients aged 1 to 21 years. Doses of 1000, 1200 and 1500 mg/m(2) were administered for 3 weeks. Subsequently, gemcitabine was given for only 2 consecutive weeks at 1500, 1800, and 2100 mg/m(2). Plasma concentrations of gemcitabine and its metabolite, 2'2'-difluorodeoxyuridine, were measured in 28 patients.

Results: Forty patients who received 132 courses of gemcitabine were assessable for toxicity. The maximum tolerated dose of gemcitabine given weekly for 3 weeks was 1200 mg/m(2). Dose-limiting toxicity was not seen in one-third of children treated at any doses given for 2 weeks. The major toxicity was myelosuppression in three of five patients at 1500 mg/m(2) for 3 weeks, and one of seven patients at 1800 mg/m(2) for 2 weeks. Other serious adverse events were somnolence, fever and hypotension, and rash in three patients. Gemcitabine plasma concentration-time data were fit to a one- (n = 5) or two-compartment (n = 23) open model. Mean gemcitabine clearance and half-life values were 2140 mL/min/m(2) and 13.7 minutes, respectively. One patient with pancreatic cancer had a partial response. Seven patients had stable disease for 2 to 17 months.

Conclusion: Gemcitabine given by 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks was tolerated well by children at doses of 2100 mg/m(2) and 1200 mg/m(2), respectively.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adolescent
  • Adult
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Child, Preschool
  • Deoxycytidine / administration & dosage*
  • Deoxycytidine / adverse effects*
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacokinetics
  • Drug Administration Schedule
  • Female
  • Half-Life
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Neoplasms / drug therapy*


  • Antimetabolites, Antineoplastic
  • Deoxycytidine
  • gemcitabine